Week Of Traumatic Brain Injury Research Articles

Identifying Migraine Phenotype Post Traumatic Headache (MPTH) to Guide Overall Recovery From Traumatic Brain Injury.

Objective: The primary aim of this study is to develop an easy way to identify migraine phenotype posttraumatic headache (MPTH) in children with traumatic brain injury, to treat headache in traumatic brain injury effectively, and to promote faster recovery from traumatic brain injury symptoms overall. Methods: We evaluated youth aged 7-20 years in a pediatric neurology traumatic brain injury (TBI) clinic, assigning a migraine phenotype for post-traumatic headache (MPTH) at the initial visit with the 3-item ID Migraine Screener. We stratified the sample by early (≤6 weeks) and late (>6 weeks) presenters, using days to recovery from concussion symptoms as the primary outcome variable. Results: 397 youth were assessed; 54% were female. Median age was 15.1 years (range 7.0-20.4 years), and 34% of the sample had sports-related injuries. Migraine phenotype for posttraumatic headache (MPTH) was assigned to 56.1% of those seen within 6 weeks of traumatic brain injury and 50.7% of those seen after the 6-week mark. Irrespective of whether they were early or late presenters to our clinic, patients with migraine phenotype (MPTH) took longer to recover from traumatic brain injury than those with posttraumatic headache (PTH) alone. Log rank test indicated that the survival (ie, recovery) distributions between those with migraine phenotype posttraumatic headache (MPTH) and those with posttraumatic headache (PTH) were statistically different, χ2(3) = 50.186 (P < .001). Conclusions: Early identification of migraine phenotype posttraumatic headache (MPTH) following concussion can help guide more effective treatment of headache in traumatic brain injury and provide a road map for the trajectory of recovery from traumatic brain injury symptoms. It will also help us understand better the mechanisms that underlie conversion to persistent posttraumatic headache and chronic migraine after traumatic brain injury.

Serum melatonin levels in predicting mortality in patients with severe traumatic brain injury

PurposeA secondary brain injury could appear after traumatic brain injury (TBI) due to neuroinflammation, oxidation and apoptosis. Higher levels of serum melatonin have been found on admission for TBI in non-surviving than in surviving patients. Thus, the objective of this study was to know serum melatonin levels during the first week of TBI in surviving and non-surviving patients, and to know if serum melatonin levels during the first week of TBI can be used to predict mortality. MethodsPatients with an isolated and severe TBI were included; that is, if they scored < 10 points in non-cranial aspects of Injury Severity Score and < 9 points in the Glasgow Coma Scale. We measured serum melatonin concentrations at days 1, 4 and 8 of TBI. Thirty-day mortality was the end-point study. ResultsLower serum melatonin levels were found in the surviving patients (n = 90) than in the non-survivors (n = 34) on days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.02) of TBI. Serum melatonin concentrations on days 1, 4, and 8 of TBI had an area under curve (95% Confidence Interval) for the prediction of 30-day mortality of 0.85 (0.77-0.91; p < 0.001), 0.82 (0.74–0.89; p < 0.001) and 0.71 (0.61–0.79; p = 0.06) respectively. ConclusionsThe new findings of this study were the presence of higher levels of serum melatonin on days 1, 4 and 8 of TBI in non-survivors than in survivors, and the ability to predict 30-day mortality for serum melatonin levels measured at these time points. However, more research is necessary to confirm our results.

Intramuscular insulin-like growth factor-1 gene therapy modulates reactive microglia after traumatic brain injury

Reactive gliosis is a key feature and an important pathophysiological mechanism underlying chronic neurodegeneration following traumatic brain injury (TBI). In this study, we have explored the effects of intramuscular IGF-1 gene therapy on reactive gliosis and functional outcome after an injury of the cerebral cortex. Young adult male rats were intramuscularly injected with a recombinant adenoviral construct harboring the cDNA of human IGF-1 (RAd-IGF1), with a control vector expressing green fluorescent protein (RAd-GFP) or PBS as control. Three weeks after the intramuscular injections of adenoviral vectors, animals were subjected to a unilateral penetrating brain injury. The data revealed that RAd-IGF1 gene therapy significantly increased serum IGF1 levels and improved working memory performance after one week of TBI as compared to PBS or RAd-GFP lesioned animals. At the same time, when we analyzed the effects of therapy on glial scar formation, the treatment with RAd-IGF1 did not modify the number of glial fibrillary acidic protein (GFAP) positive cells, but we observed a decrease in vimentin immunoreactive astrocytes at 7 days post-lesion in the injured hemisphere compared to RAd-GFP group. Moreover, IGF-1 gene therapy reduced the number of Iba1+ cells with reactive phenotype and the number of MHCII + cells in the injured hemisphere. These results suggest that intramuscular IGF-1 gene therapy may represent a new approach to prevent traumatic brain injury outcomes in rats.

Serum caspase-3 levels during the first week of traumatic brain injury

ObjectiveConfluence between the intrinsic and extrinsic apoptosis pathways is reached at the point of caspase-3 activation, which induces death cell. Higher serum caspase-3 levels have been recorded on day 1 of traumatic brain injury (TBI) in 30-day non-survivors compared to survivors. The objectives of this study therefore were to determine whether serum caspase-3 levels are persistently higher in non-survivors than in survivors, and whether these levels may be used to predict 30-day mortality. DesignA prospective observational study was carried out. SettingSix Spanish Intensive Care Units. PatientsPatients with severe isolated TBI (defined as Glasgow Coma Scale <9 points and non-cranial Injury Severity Score <10 points). InterventionsSerum caspase-3 concentrations were measured on days 1, 4 and 8 of TBI. Main variables of interestThirty-day mortality was considered as the study endpoint. ResultsIn comparison with non-survivors (n=34), 30-day survivors (n=90) showed lower serum caspase-3 levels on days 1 (p=0.001), 4 (p<0.001) and 8 (p<0.001) of TBI. Analysis of the ROC curves showed serum caspase-3 concentrations on days 1, 4 and 8 of TBI to have an AUC (95% CI) in predicting 30-day mortality of 0.70 (0.61–0.78; p=0.001), 0.83 (0.74–0.89; p<0.001) and 0.87 (0.79–0.93; p<0.001), respectively. ConclusionsThe novel findings of our study were that serum caspase-3 levels during the first week of TBI were lower in survivors and could predict 30-day mortality.

High-Sensitivity C-Reactive Protein is a Prognostic Biomarker of Six-Month Disability after Traumatic Brain Injury: Results from the TRACK-TBI Study.

Systemic inflammation impacts outcome after traumatic brain injury (TBI), but most TBI biomarker studies have focused on brain-specific proteins. C-reactive protein (CRP) is a widely used biomarker of inflammation with potential as a prognostic biomarker after TBI. The Transforming Research and Clinical Knowledge in Traumatic Brain Injury (TRACK-TBI) study prospectively enrolled TBI patients within 24 h of injury, as well as orthopedic injury and uninjured controls; biospecimens were collected at enrollment. A subset of hospitalized participants had blood collected on day 3, day 5, and 2 weeks. High-sensitivity CRP (hsCRP) and glial fibrillary acidic protein (GFAP) were measured. Receiver operating characteristic analysis was used to evaluate the prognostic ability of hsCRP for 6-month outcome, using the Glasgow Outcome Scale-Extended (GOSE). We included 1206 TBI subjects, 122 orthopedic trauma controls (OTCs), and 209 healthy controls (HCs). Longitudinal biomarker sampling was performed in 254 hospitalized TBI subjects and 19 OTCs. hsCRP rose between days 1 and 5 for TBI and OTC subjects, and fell by 2 weeks, but remained elevated compared with HCs (p < 0.001). Longitudinally, hsCRP was significantly higher in the first 2 weeks for subjects with death/severe disability (GOSE <5) compared with those with moderate disability/good recovery (GOSE ≥5); AUC was highest at 2 weeks (AUC = 0.892). Combining hsCRP and GFAP at 2 weeks produced AUC = 0.939 for prediction of disability. Serum hsCRP measured within 2 weeks of TBI is a prognostic biomarker for disability 6 months later. hsCRP may have utility as a biomarker of target engagement for anti-inflammatory therapies.

Red blood cell distribution width as mortality biomarker in patients with traumatic brain injury.

One study found higher red blood cell distribution width (RDW) on the admission of traumatic brain injury (TBI) in non-surviving patients; however, a regression analysis was not carried out to establish an association between RDW and TBI mortality. Thus, the objectives of this study were to determine whether there is an association between RDW and TBI mortality, and to describe the temporal profile of RDW during the first week. Isolated (< 10 points in non-cranial aspects of Injury Severity Score) and severe (< 9 points in Glasgow Coma Scale) TBI patients were included. RDW at days 1, 4, and 8 of TBI were determined. The end-point study was 30-day mortality. Ninety-seven surviving patients compared to the 38 non-surviving patients had higher RDW at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p < 0.001). The area under the curve (95% CI) for prediction of mortality by RDW at days 1, 4, and 8 was 0.81 (0.73-0.87; p < 0.001), 0.92 (0.85-0.96; p < 0.001) and 0.94 (0.88-0.98; p < 0.001). Regression analysis showed an association between RDW and mortality (odds ratio = 1.778; 95% CI 1.312-2.409; p < 0.001). The association found between RDW on admission and mortality is the main new finding of our study. Regarding the temporal profile of RDW, the fact that RDW during the first week of TBI may help in estimating prognosis is another interesting finding of our study.

Traumatic Brain Injury Patients Mortality and Serum Total Antioxidant Capacity.

Objective: Oxidation is involved in secondary brain injury after traumatic brain injury (TBI). Increased concentrations of total antioxidant capacity (TAC) in blood at the time of admission for TBI have been found in non-surviving patients. The main objective of this study was to determine the role of serum TAC levels at any time during the first week of TBI for the prediction of early mortality. Methods: Isolated (<10 points in non-cranial aspects of Injury Severity Score) and severe (<9 points in Glasgow Coma Scale) TBI patients were included. Serum TAC concentrations at days 1, 4, and 8 of TBI were determined. The end-point study was 30-day mortality. Results: Higher serum TAC levels at days 1 (p < 0.001), 4 (p < 0.001), and 8 (p = 0.002) of TBI were found in non-surviving (n = 34) than in surviving patients (n = 90). The area under curve (95% Confidence Interval) for prediction of 30-day mortality by serum TAC concentrations at days 1, 4, and 8 of TBI were 0.79 (0.71–0.86; p < 0.001), 0.87 (0.79–0.93; p < 0.001), and 0.76 (0.67–0.84; p = 0.006) respectively. Conclusions: The novelty of our study was the ability to predict 30-day mortality by serum TAC concentrations at any time during the first week of TBI.

Serum caspase-3 levels during the first week of traumatic brain injury.

Confluence between the intrinsic and extrinsic apoptosis pathways is reached at the point of caspase-3 activation, which induces death cell. Higher serum caspase-3 levels have been recorded on day 1 of traumatic brain injury (TBI) in 30-day non-survivors compared to survivors. The objectives of this study therefore were to determine whether serum caspase-3 levels are persistently higher in non-survivors than in survivors, and whether these levels may be used to predict 30-day mortality. A prospective observational study was carried out. Six Spanish Intensive Care Units. Patients with severe isolated TBI (defined as Glasgow Coma Scale <9 points and non-cranial Injury Severity Score <10 points). Serum caspase-3 concentrations were measured on days 1, 4 and 8 of TBI. Thirty-day mortality was considered as the study endpoint. In comparison with non-survivors (n=34), 30-day survivors (n=90) showed lower serum caspase-3 levels on days 1 (p=0.001), 4 (p<0.001) and 8 (p<0.001) of TBI. Analysis of the ROC curves showed serum caspase-3 concentrations on days 1, 4 and 8 of TBI to have an AUC (95% CI) in predicting 30-day mortality of 0.70 (0.61-0.78; p=0.001), 0.83 (0.74-0.89; p<0.001) and 0.87 (0.79-0.93; p<0.001), respectively. The novel findings of our study were that serum caspase-3 levels during the first week of TBI were lower in survivors and could predict 30-day mortality.

High Serum Caspase-Cleaved Cytokeratin-18 Levels and Mortality of Traumatic Brain Injury Patients.

Objective: Apoptosis increases in traumatic brain injury (TBI). Caspase-cleaved cytokeratin (CCCK)-18 in blood during apoptosis could appear. At the time of admission due to TBI, higher blood CCCK-18 levels were found in non-surviving than in surviving patients. Therefore, the objective of our study was to analyze whether serum CCCK-18 levels determined during the first week after TBI could predict early mortality (at 30 days). Methods: Severe TBI patients were included (considering severe when Glasgow Coma Scale < 9) in this observational and multicentre study. Serum CCCK-18 levels were determined at day 1 of TBI, and at days 4 and 8 after TBI. Results: Serum CCCK-18 levels at day 1 of TBI, and in the days 4 and 8 after TBI were higher (p < 0.001) in non-surviving than in surviving patients (34 and 90 patients, respectively) and could predict early mortality (p < 0.001 in the area under the curve). Conclusions: The new findings from our study were that serum CCCK-18 levels at any moment of the first week of TBI were higher in non-surviving patients and were able to predict early mortality.

Persistently High Serum Substance P Levels and Early Mortality in Patients with Severe Traumatic Brain Injury

Substance P is a neuropeptide belonging to the tachykinin family and is involved in neuroinflammation. In a previous study by our team, we found higher serum substance P levels on day 1 of traumatic brain injury (TBI) in nonsurviving than in surviving patients. Thus, the objective of this study was to determine whether serum substance P levels during the first week of TBI could predict early mortality. This was a multicenter, observational, and prospective study. We included patients with an isolated severe TBI, defining isolated as <9 points in non-cranial aspects of Injury Severity Score and severe as <9 points of Glasgow Coma Scale. We determined serum substance P concentrations at days 1, 4, and 8 of TBI. We performed receiver operating characteristic analyses to determine the capacity of serum substance P levels at day 1, 4, and 8 of TBI to predict 30-day mortality. Nonsurviving (n= 34) compared with surviving patients (n= 90) had greater serum substance P levels on day 1 (P < 0.001), 4 (P < 0.001), and 8 (P < 0.001) of TBI. The areas under curve of serum substance P concentrations at days 1, 4, and 8 of TBI to predict 30-day mortality were 76% (P < 0.001), 87% (P < 0.001), and 89% (P < 0.001), respectively. The new finding of our study is that the presence of elevated serum substance P levels during the first week of TBI is associated with increased mortality.

Nonsurviving Patients with Severe Traumatic Brain Injury Have Maintained High Serum sCD40L Levels

Soluble cluster of differentiation 40 ligand (sCD40L) is a member of the tumor necrosis factor family with proinflamatory and procoagulant effects. A previous study found higher serum sCD40L levels at day 1 of traumatic brain injury (TBI) in nonsurviving than surviving patients. Thus the objective of this study was to compare serum sCD40L levels during the first week of a severe TBI between surviving and nonsurviving patients and to determine whether it could be used as a mortality predictor biomarker. In this multicenter study severe TBI patients (with Glasgow Coma Scale score <9) with an Injury Severity Score in noncranial item <9 were included. Serum sCD40L concentrations at days 1, 4, and 8 of TBI were determined. We performed receiver operating characteristic analyses to determine the capacity of 30-day TBI mortality prediction by serum sCD40L levels at days 1, 4, and 8 of TBI. We found that nonsurviving (n= 34) patients in comparison with surviving (n= 90) patients had higher sCD40L levels on days 1 (P < 0.001), 4 (P= 0.004), and 8 (P<0.001) of TBI. We also found that the areas under curve of serum sCD40L concentrations at days 1, 4, and 8 of TBI to 30-day mortality prediction were 82% (P < 0.001), 72% (P=0.01) and 83% (P < 0.001), respectively. The existence of higher serum sCD40L levels in nonsurviving than surviving patients during the first week of TBI and fact that serum sCD40L levels during the first week of TBI can be used as a mortality predictor biomarker are the new findings of our study.

Intraoperative Secondary Insults During Orthopedic Surgery in Traumatic Brain Injury

Secondary insults worsen outcomes after traumatic brain injury (TBI). However, data on intraoperative secondary insults are sparse. The primary aim of this study was to examine the prevalence of intraoperative secondary insults during orthopedic surgery after moderate-severe TBI. We also examined the impact of intraoperative secondary insults on postoperative head computed tomographic scan, intracranial pressure (ICP), and escalation of care within 24 hours of surgery. We reviewed medical records of TBI patients 18 years and above with Glasgow Coma Scale score <13 who underwent single orthopedic surgery within 2 weeks of TBI. Secondary insults examined were: systemic hypotension (systolic blood pressure<90 mm Hg), intracranial hypertension (ICP>20 mm Hg), cerebral hypotension (cerebral perfusion pressure<50 mm Hg), hypercarbia (end-tidal CO2>40 mm Hg), hypocarbia (end-tidal CO2<30 mm Hg in absence of intracranial hypertension), hyperglycemia (glucose>200 mg/dL), hypoglycemia (glucose<60 mg/dL), and hyperthermia (temperature >38°C). A total of 78 patients (41 [18 to 81] y, 68% male) met the inclusion criteria. The most common intraoperative secondary insults were systemic hypotension (60%), intracranial hypertension and cerebral hypotension (50% and 45%, respectively, in patients with ICP monitoring), hypercarbia (32%), and hypocarbia (29%). Intraoperative secondary insults were associated with worsening of head computed tomography, postoperative decrease of Glasgow Coma Scale score by ≥2, and escalation of care. After Bonferroni correction, association between cerebral hypotension and postoperative escalation of care remained significant (P<0.001). Intraoperative secondary insults were common during orthopedic surgery in patients with TBI and were associated with postoperative escalation of care. Strategies to minimize intraoperative secondary insults are needed.

Identifying Important Attributes for Prognostic Prediction in Traumatic Brain Injury Patients. A Hybrid Method of Decision Tree and Neural Network.

Generally, traumatic brain injury (TBI) patients do not have a stable condition, particularly after the first week of TBI. Hence, indicating the attributes in prognosis through a prediction model is of utmost importance since it helps caregivers with treatment-decision options, or prepares the relatives for the most-likely outcome. This study attempted to determine and order the attributes in prognostic prediction in TBI patients, based on early clinical findings. A hybrid method was employed, which combines a decision tree (DT) and an artificial neural network (ANN) in order to improve the modeling process. The DT approach was applied as the initial analysis of the network architecture to increase accuracy in prediction. Afterwards, the ANN structure was mapped from the initial DT based on a part of the data. Subsequently, the designed network was trained and validated by the remaining data. 5-fold cross-validation method was applied to train the network. The area under the receiver operating characteristic (ROC) curve, sensitivity, specificity, and accuracy rate were utilized as performance measures. The important attributes were then determined from the trained network using two methods: change of mean squared error (MSE), and sensitivity analysis (SA). The hybrid method offered better results compared to the DT method. The accuracy rate of 86.3 % vs. 82.2 %, sensitivity value of 55.1 % vs. 47.6 %, specificity value of 93.6 % vs. 91.1 %, and the area under the ROC curve of 0.705 vs. 0.695 were achieved for the hybrid method and DT, respectively. However, the attributes' order by DT method was more consistent with the clinical literature. The combination of different modeling methods can enhance their performance. However, it may create some complexities in computations and interpretations. The outcome of the present study could deliver some useful hints in prognostic prediction on the basis of early clinical findings for TBI patients.

Neuropsychological performance of youth with secondary attention-deficit/hyperactivity disorder 6- and 12-months after traumatic brain injury.

The present study compared executive dysfunction among children with attention-deficit/hyperactivity disorder (ADHD) after traumatic brain injury (TBI), also called secondary ADHD (S-ADHD), pre-injury ADHD and children with TBI only (i.e., no ADHD). Youth aged 6-16 years admitted for TBI to five trauma centers were enrolled (n=177) and evaluated with a semi-structured psychiatric interview scheduled on three occasions (within 2 weeks of TBI, i.e., baseline assessment for pre-injury status; 6-months and 12-months post-TBI). This permitted the determination of 6- and 12-month post-injury classifications of membership in three mutually exclusive groups (S-ADHD; pre-injury ADHD; TBI-only). Several executive control measures were administered. Unremitted S-ADHD was present in 17/141 (12%) children at the 6-month assessment, and in 14/125 (11%) children at 12-months post-injury. The study found that children with S-ADHD exhibited deficient working memory, attention, and psychomotor speed as compared to children with pre-injury ADHD. Furthermore, the children with S-ADHD and the children with TBI-only were impaired compared to the children with pre-injury ADHD with regard to planning. No group differences related to response inhibition emerged. Age, but not injury severity, gender, or adaptive functioning was related to executive function outcome. Neuropsychological sequelae distinguish among children who develop S-ADHD following TBI and those with TBI only. Moreover, there appears to be a different pattern of executive control performance in those who develop S-ADHD than in children with pre-injury ADHD suggesting that differences exist in the underlying neural mechanisms that define each disorder, underscoring the need to identify targeted treatment interventions.